chapter 10 micro

pathogenesis

the process of disease development

what do some microbiota do for us in return for us giving a place for them to live

-manufacture vitamins for us
-compete with potential pathogens
-promote immune system maturation

pathogens

disease-causing microbes

dysbiosis

microbiota disruption

what are two examples of an opportunistic pathogen

-Escherichia coli in the appendix enters the abdominal cavity (ferments and bursts)

-weakened immune system allows yeast infections

tropism

preference of a pathogen for a specific host (and even a specific tissue within the host)

pathogenicity

the ability of a microbe to cause disease

virulence

describes the degree of or extend of disease that a pathogen causes

virulence factors

ways pathogens overcome our defenses (e.g. features that help microbes adhere to host cells, invade host tissues, etc.)

what are classic virulence factors

toxicity, aggressiveness, and transmission

how many virulence factors damage host cells

-by directly damaging host cells (actually break down the tissues)

-by provoking dangerous immune responses (make our immune system hurt us)

what must happen for a pathogen to persist in a population

-it must endure over time

-it must find a balance between breaking down defenses and living within an individual host

agents that are transmitted from person to person and kill hosts quickly usually...

-cause high mortality outbreaks
-are short in duration
-are geographically isolated (because people don't go around it, they stay away from it)

why do pathogens only develop a keep a particular virulence factor when it benefits them

because making virulence factors requires an energy investment

ID50 (infectious dose-50)

the number of cells or virions needed to establish an infection in 50% of exposed hosts

do more infectious pathogens have a higher or lower ID50

lower

LD50 (lethal dose-50)

the amount of toxin needed to kill 50% of affected hosts that are not treated

ID50 and LD50 can change based on what

-species affected
-host's immune fitness
-route of exposure

why are LD50 and ID50 measures not a perfect predictor of what would occur in people

because the values usually come from animal studies

toxins

molecules that generate a range of adverse host effects such as tissue damage and suppressed immune response

toxigenic

microbe that make toxins

toxemia

toxins in the blood

what are the two classes of toxins

endotoxins and exotoxins

what type of cells produce endotoxins

gram-negative

what are endotoxins

the lipid A region of lipopolysaccharide (LPS is found in the outer membrane of gram-negative bacteria)

what are exotoxins

toxic, soluble proteins that are produced by both gram positive and gram negative bacteria

-bacterial metabolites released from their cytoplasm to the extracellular medium during their normal cell cycle function

when are endotoxins released into the body

mainly from the cell wall when bacteria die but a small amount when bacteria divide

where are exotoxins released from

actively growing bacteria

what are endotoxins made of? exotoxins?

endotoxins \= lipid

exotoxins \= protein

are there vaccines for endotoxins? exotoxins?

endotoxins- no

exotoxins- yes (some)

do endotoxins cause a fever? exotoxins?

endotoxins- yes

exotoxins- sometimes (certain superantigens)

can endotoxins be neutralized in a patient? exotoxins?

endotoxins- no

exotoxins- yes (some)

what is the toxicity level of endotoxins? exotoxins?

endotoxins: lower (relatively high LD50)

exotoxins: higher (many have a low LD50)

can can endotoxins cause if present in sufficient quantities

septic shock

endotoxemia

endotoxin in the bloodstream

how can endotoxins enter the bloodstream

-localized infections
-systemic infections
-gram negative microbiota that are introduced to areas where they don't belong
-surgery complications

why can't we really get rid of endotoxins

they are not readily neutralized and there are no vaccines to protect against them

what is are ways to classify exotoxins

-named based on the organism that makes it or the type of cells it targets

neurotoxins

affect the nervous system

enterotoxins

target the GI tract

hepatotoxins

affect the liver

exotoxins are classified into three main families based on what

their mode of action/ what it does to the cell

type I exotoxins

-membrane acting extracellular toxins
-bind to target via receptors on the surface
-propagate a signaling cascade via the receptor
-evokes changes in gene expression (turn genes on or off)
-leads to diverse outcomes (range from temporarily altered cell physiology to cell death)

-(toxin binds at host plasma membrane to generate a signal that generates effects; toxin doesn't enter the cell)

what are examples of type I exotoxins

-heat stable enterotoxins made by enterotoxigenic E. coli

-superantigens

what are superantigens

-a group of endotoxins that overstimulate the immune system to cause massive inflammation that harms the host

-they are also pyrogens (they stimulate the hypothalamus to turn up the thermostat to cause a fever)

type II exotoxins

-membrane damaging toxins
-disrupt the host cell plasma membrane
-forms pores or removes phosphate head groups from phospholipids
-destabilizes the membrane
-causes cell lysis

-(toxins disrupt host cell membranes by forming pores or breaking down membrane lipids)

what is an example of a bacteria that produces a type II exotoxin

Clostridium perfingens
-can cause gas gangrene (dissolves tissues)
-common with diabetes
-limbs can just fall off
-Alpha toxin (lecithinase)
-Kappa toxin (collagenase)
-Mu toxin (hyaluronidase)

what does alpha toxin (lecithinase) do

increases the permeability of capillaries and muscle cells by breaking down lecithin in cytoplasmic membranes

what does kappa toxin (collagenase) do

breaks down supportive connective tissue

what does mu toxin (hyaluronidase) do

breaks down the tissue cement that holds cells together in tissue

leukotoxins

-pore forming toxins that cause lysis of white blood cells

what organisms produce leukotoxins

S. aureus and S. pyogenes

tyle III exotoxins

-intracellular toxins
-bind to a receptor and enter the cell
-most exotoxins in this group are AB toxins

(1. binding portion (B) of toxins binds plasma membrane, 2. toxin enters cell, often by endocytosis, 3. active portion (A) enters the host cell and exerts an effect)

toxoid

an inactivated form of a toxin

what are the five steps to infection

1. enter the host
2. adhere to the host
3. invade tissues and obtain nutrients
4. replicate while warding off immune defenses
5. transmit to a new host

portal of entry

any site that a pathogen uses to enter the ost

what is the most common portal of entry

mucous membranes

T or F

the portal of entry is the site where the disease develops, but not necessarily the only or the main site affected

true

integumentary system

-the largest body system
-consists of skin, hair, nails, and associated glands
-blocks most microbes

respiratory tract

-the most common portal of entry
-a pathogen that enters through the respiratory tract does not necessarily establish an infection there

gastrointestinal (GI) tract

-frequently have fecal-oral transmission
-invade the mucosal surfaces of the GI tract

urogenital tract

-most sexually transmitted pathogens enter through the mucosal lining of the vagina or cervix in women or the urethra in men
-certain sexually transmitted pathogens invade through the skin of the genitalia

transplacental entry

some pathogens exhibit vertical transmission by transplacental entry

what pathogen enters the body through the otic route (ear)

P. aeruginosa (Swimmer's ear)

what pathogens enter through the respiratory mucosa

measles and influenza

what pathogens enter through GI mucosa

cholera, salmonella, and C. difficile

what pathogens enter through the urogenital/reproductive system

genital: gonorrhea, chlamydia, certain papillomaviruses

urinary: E. coli

what pathogens enter ocularly (through the eye)

various bacteria and viruses; causes conjunctivitis

what infection enters through the skin

S. aureus (wound infection)

what pathogens enter parenterally (through needles)

Hepatitis B and C

what pathogens enter transplacentally

HIV, rubella, toxoplasmosis

adhesions

virulence factors used to stick to host cells in a specific or nonspecific manner

what are examples of bacterial adhesions

cell wall components, capsules, fimbriae, and pili

fimbriae or pili

extracellular hair-like appendages that bind carbohydrates on host cells

what pathogens use fimbriae or pili for adhesion

E. coli (urinary system infections)

Pseudomonas aeruginosa (respiratory and wound infections)

Neisseria gonorrhoeae (gonorrhea)

Vibrio vulnificus (deep wound infections like cellulitis and necrotizing fasciitis)

sialic acid binding factors

surface molecules that bind to sialic acid (diverse acidic sugar molecules on host cells)

what are pathogens that use sialic acid binding factors to adhere to host cells

Rotaviruses (GI infections)

Influenza viruses

Aspergillus fumigatus (fungal lung infection)

Plasmodium falciparum (malarial parasite)

heparan and heparin sulfate binding factors

factors that target host cell heparan and heparin sulfate (acidic sugary molecules that are present in many cells and tissues)

what pathogens use heparan and heparin sulfate binding factors to adhere to host cells

Borrelia burgdorferi (Lyme disease)

Helicobacter pylori (gastric ulcers)

Human immunodeficiency virus HIV (AIDS)

Herpes simplex viruses

what rash does lyme disease cause

a target-like rash

what tick can give you lyme disease

Ixodes scapularis

fibronectin binding factors

assorted surface molecules that bind to the protein fibronectin in host epithelial tissue

what pathogens enter through fibronectin binding factors

Streptococcus pyogenes (strep throat)

Staphylococcus aureus (staph infections)

Mycobacterium tuberculosis (tuberculosis)

Clostridium difficile (infectious diarrhea)

Candida albicans (yeast infection)

what are common places for healthcare-acquired biofilm formation

implanted devices (catheters, implanted prosthetic joints, etc.) and rocky deposits in the kidneys (kidney stones) or gallbladder (gallstones)

what do many bacteria use to pre-transcriptionally control protein synthesis

quorum sensing

autoinducers

chemical messengers used by bacteria to communicate

what is quorum sensing

the ability of bacteria in a biofilm to communicate with each other and coordinate their activities

-it also allows bacteria to alter their protein synthesis in response to changes in the density of the population

following adhesion, what options does the pathogen have

-stay on the surface of the host cell
-pass through cells to invade deeper tissue
-enter cells to reside as an intracellular pathogen

cytopathic effects

structural changes in host cells that are caused by viral invasion

what are two examples of cytopathic effects

cytocidal- kill the cell

noncytocidal- damage the cell

invasins

a class of proteins associated with the penetration of pathogens into host cells

-allow pathogens to invade host tissues
-local acting factors
-usually membrane associated or secreted enzymes

what is the mechanism of action of invasins

break down host tissues

form blood clots

induce the host to uptake the pathogen

motility

what is hyaluronidase

an invasin that degrades connective tissue; produced by Streptococci, Staphylococci, and Clostridium

what is collagenase

an invasin that dissolves collagen, an important structural protein in tissues, allowing for invasion of new host tissues; produced by Clostridium

what is neuraminidase

an invasin that degrades neuraminic acid (NA) of the intestinal mucosa, which has important roles in regulating host cell communications and membrane transport; produced by vibrio, cholera, and shigella

what tools do pathogens use to obtain nutrients

siderophores and extracellular enzymes

transferrin

a protein that binds to iron and shittles it to tissues

siderophores

iron-binding complexes that snatch iron from transferrin or RBCs for their own use

extracellular enzymes

enzymes that break down nutrients in the local environment which allows pathogens to scavenge nutrients as they damage host tissues

what are two examples of extracellular enzymes

lipases: break down lipids

proteases- break down proteins